Published January 30, 2013
Arin Bhattacharjee, PhD, assistant professor of pharmacology and toxicology, will use a $1.7 million grant to study mechanisms underlying peripheral neuropathy, a common symptom of diabetes that does not respond to existing pain medication.
The five-year project, funded through the National Institute of Neurological Disorders and Stroke, will explore whether an understudied family of potassium channels could be targeted to treat neuropathic pain.
Bhattacharjee and his colleagues are trying to determine whether high glucose stress reduces activity in sodium-activated potassium channels.
In previous studies, they discovered that these channels, found at high levels in pain-sensing neurons, prevent the neurons from repetitively discharging.
During the current study, the researchers will look for signs of a key enzyme—p38 MAP Kinase—that may directly alter the properties of ion channels, especially potassium channels.
The researchers also seek to understand the molecular composition of sodium-activated potassium channels required to keep pain-sensing neurons quiet.
Finally, they will study how mice missing a subunit of these channels respond to hyperglycemia.
In diabetes, chronic high blood glucose directly damages neurons. These neurons become hyperexcitable, discharging more often than normal neurons and causing feelings of intense pain.
How hyperglycemia causes this effect is unknown, but p38 MAP Kinase may play a role.
“The molecular controls of excitability in sensory neurons are still unresolved, and sensory neuron hyperexcitability is essential in mediating the neuropathic process,” Bhattacharjee says.